The neuropathology core is maintained by a professional staff of Lawrence Hansen, M.D. and Eliezer Masliah, M.D. Its functions include neuropathologic and neurochemical analyses of autopsy specimens from patients clinical evaluated at the ADRC, and maintenance of a brain tissue bank of frozen and fixed material from such clinically and neuropathologically characterized patients. On the basis of the past several years experience, we anticipate receiving 50-60 brains annually, mostly originating from the ADRC. In may cases, rapid autopsies (within 8 hours of death) allow fresh brain tissues to be distributed to ADRC affiliated research laboratories for use in RNA biochemistry, in situ hybridization/autoradiography, and immunohistochemistry. After removing the appropriate fresh tissue blocks for such studies, the right hemibrain is frozen at 70. This specimen is utilized for neurochemical measurements of choline acetyltransferase, somatostatin, and synaptophysin, as well as for western blot analyses to determine antibody sensitivities and specificities for correlations with various immunohistochemical studies. Frozen brain tissue is also available for distribution to other ADRC investigators. Neuropathologic studies are carried out on the formalin fixed left hemibrain, and involve multiple stains on multiple blocks from all parts of the brain. Diagnoses are established by the location and concentration of plaques and tangles as quantified with thioflavin and Bielschowsky preparations. We will also neuropathologically stage the extent of Alzheimer disease pathology in Alzheimer cases and in our elderly controls using the staging classification of Braak and Braak. Other diagnoses are added or ruled- out. Lewy body disease is evaluated with both H&E and anti-ubiquitin immunohistochemical preparations. Cresyl violet stained section are used for neocortical cell counting by image analysis. All data are recorded in the computerized data base of this core, as well as in the ADRC main computer.